Role of α 1 ‐adrenoceptor subtypes in the effects of methylenedioxy methamphetamine (MDMA) on body temperature in the mouse

Background and purpose: We have investigated the ability of α 1 ‐adrenoceptor antagonists to affect the hyperthermia produced by methylenedioxy methamphetamine (MDMA) in conscious mice. Experimental approach: Mice were implanted with temperature probes under ether anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg −1 ) was administered subcutaneously 30 min after vehicle or test antagonist or combination of antagonists and effects on body temperature monitored. Key results: Following vehicle, MDMA produced a hyperthermia, reaching a maximum increase of 1.8 °C at 140 min. Prazosin (0.1 mg kg −1 ) revealed an early significant hypothermia to MDMA of −1.94 °C. The α 1A ‐adrenoceptor antagonist RS 100329 (0.1 mg kg −1 ), or the α 1D ‐adrenoceptor antagonist BMY 7378 (0.5 mg kg −1 ) given alone, did not reveal a hypothermia to MDMA, but the combination of the two antagonists revealed a significant hypothermia to MDMA. The putative α 1B ‐adrenoceptor anatagonist cyclazosin (1 mg kg −1 ) also revealed a significant hypothermia to MDMA, but actions of cyclazosin at the other α 1 ‐adrenoceptor subtypes cannot be excluded. Conclusions and implications: More than one subtype of α 1 ‐adrenoceptor is involved in a component of the hyperthermic response to MDMA in mouse, probably both α 1A ‐ and α 1D ‐adrenoceptors, and removal of this α 1 ‐adrenoceptor‐mediated component reveals an initial hypothermia. British Journal of Pharmacology (2008) 153 , 591–597; doi: 10.1038/sj.bjp.0707590 ; published online 26 November 2007